Alpha 4 Beta 7 Integrin Expression And Blockade In Pediatric And Young Adult Gastrointestinal Graft-Versus-Host Disease

Background We hypothesized that alpha 4 beta 7 integrin expression on effector memory T cells (TEMs) would be elevated in pediatric hematopoietic stem cell transplant (HSCT) patients before and at diagnosis of acute gastrointestinal graft-versus-host disease (GI GVHD) symptoms compared to patients without GVHD, and that clinical blockade of alpha 4 beta 7 integrin with vedolizumab would be effective in pediatric GI GVHD.Methods We analyzed surface expression of alpha 4 beta 7 integrin on T cells from 48 pediatric allogeneic HSCT recipients from our biorepository with known clinical outcomes as follows: acute GI GVHD (n = 22), isolated skin GVHD (n = 12), and no GVHD (n = 14). T-cell analyses were performed 1 week before and at GVHD diagnosis in patients with GVHD, and day +30 after HSCT in patients without GVHD. We describe clinical outcomes of seven additional patients, different from above-described 48 patients, who received vedolizumab (anti-alpha 4 beta 7 integrin antibody) for the treatment of steroid-refractory acute GI GVHD.Results Expression of alpha 4 beta 7 integrin on CD8+ TEMs was upregulated in patients with GI GVHD compared to the no GI GVHD (skin GVHD + no GVHD) group 1 week prior to clinical symptoms (p = .02) and at acute GI GVHD diagnosis (p = .05). Four of seven treated patients with clinical steroid-refractory acute GI GVHD were evaluable for response to vedolizumab. One patient had a complete response at day +28, while two had a partial response, and one had no response. No adverse effects directly attributable to vedolizumab were observed.Conclusion Our data suggest a rationale for the blockade of alpha 4 beta 7 integrin for acute GI GVHD management in children.